Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

Nucleic acid aptamers are oligonucleotide sequences screened by an in vitro methodology called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Known as "chemical antibodies", aptamers can achieve specific recognition towards the targets through conformational changes with high affinity, and possess multiple attractive features including, but not limited to, easy and inexpensive to prepare by chemical synthesis, relatively stable and low batch-to-batch variability, easy modification and signal amplification, and low immunogenicity. Now, aptamers are attracting researchers' attentions from more than 25 disciplines, and have showed great potential for application and economic benefits in disease diagnosis, environmental detection, food security, drug delivery and discovery. Although some aptamers exist naturally as the ligand-binding elements of riboswitches, SELEX is a recognized method for aptamers screening. After thirty-two years of development, a series of SELEX methods have been investigated and developed, as well as have shown unique advantages to improve sequence performances or to explore screening mechanisms. This review would mainly focus on the novel or improved SELEX methods that are available in the past five years. Firstly, we present a clear overview of the aptamer's history, features, and SELEX development. Then, we highlight the specific examples to emphasize the recent progress of SELEX methods in terms of carrier materials, technical improvements, real sample-improved screening, post-SELEX and other methods, as well as their respects of screening strategies, implementation features, screening parameters. Finally, we discuss the remaining challenges that have the potential to hinder the success of SELEX and aptamers in practical applications, and provide the suggestions and future directions for developing more convenient, efficient, and stable SELEX methods in the future. 

Recent progress of SELEX methods for screening nucleic acid aptamers.

Diabetes is a chronic illness all over the world, and is one of the fastest growing global health emergencies of the 21st century. Since diabetes is a multi-system disease requiring complex management, the comprehensive care of patients with diabetes is necessary. However, frequent testing will be problematic for patients, and the laboratory results informing health care professional may not be promptly, thereby may delay appropriate management. Therefore, the availability of point-of care testing (POCT) or near patient testing which is conducted outside of a centralized laboratory by clinical staff, for biomolecules necessary for the management of patients with diabetes, is important. Diabetes mellitus is best managed by tight glycemic control, which will be achieved by glucose monitoring. Diagnoses of diabetes are carried out based on glycated hemoglobin and blood glucose concentration. In addition to glucose, glycated protein, ketone, insulin, glucagon and incretins are being the target for POCT monitoring. Recently, varieties of biosensing principles for these diabetes biomarkers have been reported based on novel biosensing principles together with the development of novel biosensing molecules. The purpose of this study was to explore current available biosensing molecules which have been utilized for the development of POCT sensor for the molecules related with the diagnosis, managements and treatment of diabetic patients.

Current and future prospective of biosensing molecules for point-of-care sensors for diabetes biomarker

Glycated albumin (GA) has been previously introduced as a promising biomarker for glycemic monitoring in diabetes patients with thalassemia. In this study, a label-free graphene oxide (GO)-modified aptasensor was developed for the rapid detection of GA. The fabrication of the aptasensor was dependent on the covalent interaction of the amine-functionalized GA-specific aptamer with the carboxylic groups of GO. Square wave voltammetry (SWV) analysis was carried out for the measurement of GA-aptamer binding to their specific proteins. The peak current changes before and after incubation with GA protein were directly proportional to the concentration. The developed aptasensor exhibited a broad linearity (1–10,000 µg mL−1), a low detection limit (LOD) of 0.031 µg mL−1, and high selectivity for GA detection. In addition, the aptasensor was successfully applied to detect GA in both spiked and clinical serum samples. The comparison of the developed method with a commercial assay validated the reliability of the aptasensor for clinical application. Therefore, the newly developed aptasensor is a promising tool for GA measurements in diabetic patients with underlying thalassemia.

A Simple Graphene Functionalized Electrochemical Aptasensor for the Sensitive and Selective Detection of Glycated Albumin

In the last couple of decades, aptamers have been one of the preferred biomolecular recognition elements in biosensors. The platform of aptasensors (aptamer-based biosensors) is demonstrated to solve practical research problems in various areas. Aptamers and biosensors altogether gift a specific, selective, sensitive, affordable, easy to operate, robust, rapid, stable, and low sample volume analytical platform. In diagnostics, numerous review articles are published discussing the detection of various types of non-infectious and infectious diseases using aptasensors, but to the best of our knowledge, no one has reviewed the available information from the perspective of the utility of aptasensors for a full body health checkup. Therefore, to bridge this existing gap in knowledge in terms of the utility of aptasensors for full body health checkup and to provide a new perspective to the aptasensor community, in this review article, we are reviewing a battery of aptasensors, which has been utilized to detect biomarkers that correlate well with an individual's health status. Our motive in this review is to demonstrate the expansion of utility of aptasensors in routine full body checkups. Systematic Evolution of Ligands by Exponential Enrichment (SELEX), design configurations, and various detection methods employed for aptasensors are also discussed. Along with, the existing gap in the field, current challenges, and future of aptamers in diagnostics with concluding remarks are also presented in this review article. 

Aptasensors for full body health checkup

Development of a Novel ssDNA Sequence for a Glycated Human Serum Albumin and Construction of a Simple Aptasensor System Based on Reduced Graphene Oxide (rGO).

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Development of a Novel ssDNA Sequence for a Glycated Human Serum Albumin and Construction of a Simple Aptasensor System Based on Reduced Graphene Oxide (rGO).